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Assessing the Role of Anti rh-GAA in Modulating Response to ERT in a Late-Onset Pompe Disease Cohort from the Italian GSDII Study Group

  • Massimiliano FilostoEmail author
  • Stefano Cotti Piccinelli
  • Sabrina Ravaglia
  • Serenella Servidei
  • Maurizio Moggio
  • Olimpia Musumeci
  • Maria Alice Donati
  • Elena Pegoraro
  • Antonio Di Muzio
  • Lorenzo Maggi
  • Paola Tonin
  • Gianni Marrosu
  • Cristina Sancricca
  • Alberto Lerario
  • Michele Sacchini
  • Claudio Semplicini
  • Virginia Bozzoni
  • Roberta Telese
  • Silvia Bonanno
  • Rachele Piras
  • Maria Antonietta Maioli
  • Giulia Ricci
  • Liliana Vercelli
  • Anna Galvagni
  • Serena Gallo Cassarino
  • Filomena Caria
  • Tiziana Mongini
  • Gabriele Siciliano
  • Alessandro Padovani
  • Antonio Toscano
Original Research
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Abstract

Introduction

Patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy (ERT) may develop IgG antibodies against alglucosidase alpha (anti-rhGAA) in the first 3 months of treatment. The exact role of these antibodies in modulating efficacy of ERT in this group of patients is still not fully understood. To assess whether anti rh-GAA antibodies interfere with ERT efficacy, we studied a large Italian cohort of LOPD patients.

Methods

We analyzed clinical findings and performed serial measurements of IgG anti rh-GAA antibody titers from 64 LOPD patients treated with ERT. The first examination (T0) was completed on average at 17.56 months after starting ERT, while the follow-up (T1) was collected on average at 38.5 months. Differences in T0–T1 delta of the six-minute walking test (6MWT), MRC sum score (MRC), gait, stairs and chair performance (GSGC) and forced vital capacity (FVC) were considered and then related to the antibody titers.

Results

Almost 22% of the patients never developed antibodies against GAA, while 78.1% had a positive titer (31.2% patients developed a low titer, 43.8% a medium titer and 3.1% a high titer). No statistical significance was found in relating the T0–T1 delta differences and antibody titers, except for MRC sum score values in a subgroup of patients treated < 36 months, in which those with a null antibody titer showed a greater clinical improvement than patients with a positive titer.

Conclusion

Our results confirm that in a large cohort of LOPD patients, anti rh-GAA antibody generation did not significantly affect either clinical outcome or ERT efficacy. However, in the first 36 months of treatment, a possible interference of low-medium antibody titers with the clinical status could be present. Therefore, a careful and regular evaluation of antibody titers, especially in cases with evidence of clinical decline despite ERT, should be performed.

Keywords

Anti rh-GAA antibodies Glycogen storage diseases II GSD II LOPD Pompe disease 

Notes

Acknowledgements

The authors thank the participants of the study.

Funding

No funding or sponsorship was received for this study or publication of this article. The article processing charges were funded by the authors.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosures

Antonio Toscano is a member of the Pompe Global Advisory Board sustained by Sanofi Genzyme and has received reimbursement for participation in board meetings and lectures. Massimiliano Filosto has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Stefano Cotti Piccinelli has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Sabrina Ravaglia has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Serenella Servidei has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Maurizio Moggio has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Olimpia Musumeci has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Maria Alice Donati has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Elena Pegoraro has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Antonio Di Muzio has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Lorenzo Maggi has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Paola Tonin has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Gianni Marrosu has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Cristina Sancricca has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Alberto Lerario has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Michele Sacchini has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Claudio Semplicini has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Rachele Piras has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Maria Antonietta Maioli has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Giulia Ricci has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Liliana Vercelli has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Anna Galvagni has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Serena Gallo Cassarino has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Filomena Caria has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Tiziana Mongini has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Gabriele Siciliano has received reimbursement for participation in conferences, board meetings and/or lectures by Sanofi Genzyme. Virginia Bozzoni, Roberta Telese, Silvia Bonanno and Alessandro Padovani have nothing to disclose.

Compliance with Ethics Guidelines

This study was conducted in accordance with GCP and ethical principles deriving from the Declaration of Helsinki and from regulations in force for observational studies. Ethics Committee approval was not necessary as this was performed in a routine clinical setting. All the participants provided verbal informed consent to perform clinical and anti rh-GAA evaluations.

Data Availability

The data sets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Copyright information

© Springer Healthcare Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Massimiliano Filosto
    • 1
    Email author
  • Stefano Cotti Piccinelli
    • 1
  • Sabrina Ravaglia
    • 2
  • Serenella Servidei
    • 3
  • Maurizio Moggio
    • 4
  • Olimpia Musumeci
    • 5
  • Maria Alice Donati
    • 6
  • Elena Pegoraro
    • 7
  • Antonio Di Muzio
    • 8
  • Lorenzo Maggi
    • 9
  • Paola Tonin
    • 10
  • Gianni Marrosu
    • 11
  • Cristina Sancricca
    • 3
  • Alberto Lerario
    • 4
  • Michele Sacchini
    • 6
  • Claudio Semplicini
    • 7
  • Virginia Bozzoni
    • 7
  • Roberta Telese
    • 8
  • Silvia Bonanno
    • 9
  • Rachele Piras
    • 11
  • Maria Antonietta Maioli
    • 11
  • Giulia Ricci
    • 12
  • Liliana Vercelli
    • 13
  • Anna Galvagni
    • 1
  • Serena Gallo Cassarino
    • 1
  • Filomena Caria
    • 1
  • Tiziana Mongini
    • 13
  • Gabriele Siciliano
    • 12
  • Alessandro Padovani
    • 1
  • Antonio Toscano
    • 5
  1. 1.Center for Neuromuscular Diseases, Unit of NeurologyASST Spedali Civili and University of BresciaBresciaItaly
  2. 2.Emergency Neurology, IRCCS Mondino FoundationPaviaItaly
  3. 3.Institute of Neurology, Catholic University of Sacred HeartRomeItaly
  4. 4.Neuromuscular and Rare Diseases Unit, Department of NeuroscienceFondazione IRCCS Ca’ Granda, Ospedale Maggiore PoliclinicoMilanItaly
  5. 5.Department of Clinical and Experimental Medicine, UOC di Neurologia e Malattie NeuromuscolariUniversity of MessinaMessinaItaly
  6. 6.Metabolic and Neuromuscular Unit, Meyer Children HospitalUniversity of FlorenceFlorenceItaly
  7. 7.Neuromuscular Center, Department of NeurosciencesUniversity of PadovaPaduaItaly
  8. 8.Department of Neuroscience and ImagingG. d’Annunzio UniversityChietiItaly
  9. 9.Neurology IV, Neuroimmunology and Neuromuscular Diseases UnitFondazione IRCCS Istituto Neurologico “Carlo Besta”MilanItaly
  10. 10.Neurological ClinicUniversity of VeronaVeronaItaly
  11. 11.ASL8, Centro Sclerosi MultiplaCagliariItaly
  12. 12.Department of Clinical and Experimental MedicineUniversity of PisaPisaItaly
  13. 13.Department of Neurosciences Rita Levi MontalciniUniversity of TorinoTurinItaly

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